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Biomedical subjects

J Zhong

Publications and source records attributed to J Zhong.

At least 19 recordsLinked to original sources
PubMed1997

Reversible, reproducible reduction of brain water apparent diffusion coefficient by cortical electroshocks.

Rat brains were imaged after cortical electroshock pulse trains (1 ms pulses at 100 Hz) of varying durations (0.1-10 s), with diffusion-weighted echo planar imaging sequences at 2.0 T. The apparent water diffusion coefficient (ADC) decreased after either single or repeat electroshock trains. ADC reductions were observed within 6 s after the first shock. The size of the affected area of the brain increased in subsequent images during the 1st min after a 10-pulse (0.1 s) train, and also increased with the duration of electroshock trains. ADC reduction was reproducible in extent and time course after single 10-shock trains and was reversible. In the affected pixels the mean ADC reduction was 4% for a single shock train (0.1 s), and 7-8% for trains repeated once a minute, independent of electroshock train duration. The results indicate that neuronal activity associated with electrostimulation may be monitored with water diffusion measurements, and they may be useful for measuring the severity of seizure activity in patients with medically intractable epilepsy.

Animals↗
PubMed1997

The pattern of p53 and p21WAF1/CIP1 immunoreactivity in non-Hodgkin's lymphomas predicts p53 gene status.

P53 and p21WAF1/CIP1 (p21) immunostaining was performed on 92 non-Hodgkin's lymphomas (NHLs), and the staining pattern correlated with the presence or absence of p53 hot spot mutations as detected by PCR-SSCP of exons 5-8 and direct sequencing. Twenty-nine of 92 lymphomas overexpressed p53, and 17 overexpressed p21. Of the p53 overexpressing lymphomas, 14 also overexpressed p21, and none of these 14 harbored a detectable hot spot mutation. However, mutations were detected in 13 (87%) of 15 p53 overexpressing, p21 negative lymphomas. One of the 63 p53-negative lymphomas harbored a detectable hot spot mutation, and it was also negative for p21. These results demonstrate that among NHLs that overexpress p53 protein, those which also show p21 overexpression do not harbor p53 hot spot mutations, and furthermore, provide evidence that the transactivating function of p53 is retained. On the other hand, p53 overexpression in NHLs that lack p21 expression is usually indicative of p53 gene mutation.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed1997

Cytosolic Ca2+ concentration and contraction-relaxation properties of ventricular myocytes from Escherichia coli endotoxemic guinea pigs: effect of fluid resuscitation.

Hearts isolated from a guinea pig model of Escherichia coli endotoxemia exhibit decreased systolic contractile function and reduced diastolic compliance of the left ventricle within 4 h after injection of endotoxin. Fluid resuscitation prevented the endotoxin-induced decrease in diastolic compliance without affecting systolic contractile depression. Because intrinsic myocardial dysfunction after endotoxemia may result from alterations in intracellular Ca2+ handling, we tested the hypothesis that in vivo fluid resuscitation improved diastolic function by altering Ca2+ handling of the myocardium. We tested this hypothesis by measuring cell shortening and intracellular Ca2+ of ventricular myocytes isolated from endotoxemic guinea pigs. E. coli endotoxin (LPS, 1 mg/kg)-injected guinea pigs were divided into resuscitated and nonresuscitated groups. Fluid resuscitated animals received a Ringer's infusion (8 mL.kg-1.h-1) intravenously (i.v.) beginning immediately after endotoxin injection. Four hours later, ventricular myocytes were isolated enzymatically and loaded with fura-2/AM. When myocytes were field stimulated at .8 Hz, peak systolic Ca2+ transients of LPS-resuscitated (619 +/- 75 nM) and LPS-nonresuscitated (599 +/- 60 nM) myocytes were not significantly different from each other, but both were significantly less than values from control myocytes (1187 +/- 118 nM, p < .05). The percentage of cell shortening of LPS-resuscitated (6.2 +/- .9%) and LPS-nonresuscitated (6.2 +/- .3%) myocytes were also less than control (11.8 +/- .5%, p < .05). In contrast to improved diastolic compliance of fluid-resuscitated hearts, diastolic [Ca2+]i of myocytes (at .8 Hz) from LPS-resuscitated animals (138 +/- 47 nM) was not statistically different from LPS-nonresuscitated animals (129 +/- 19 nM). Diastolic values of both LPS groups were consistently lower than control value (251 +/- 38 nM, p < .05). These data suggest that improved diastolic compliance of LPS hearts following fluid resuscitation is not associated with improved myocyte contractility or myoplasmic Ca2+ handling.

Animals↗
PubMed1997

Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs.

The circulatory response to gram-negative sepsis and its experimental counterpart, endotoxemia, includes a profound dysfunction in myocardial contractility that is resident to the myocyte and associated with reduced systolic free intracellular Ca2+ concentration ([Ca2+]i). We explored the possibility that decreased systolic [Ca2+]i in endotoxemic myocytes is correlated with reduced L-type Ca2+ current (ICa,L). Ventricular myocytes were isolated from guinea pigs 4 h after an intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 4 mg/kg). Membrane potentials and Ca2+ currents were measured using whole cell patch-clamp methods. The action potential duration of endotoxemic myocytes was significantly shorter than control values (time to 50% repolarization: LPS, 314 +/- 23 ms; control, 519 +/- 36 ms, P < 0.05). Correspondingly, endotoxemic myocytes demonstrated significantly reduced peak ICa,L density (3.5 +/- 0.2 pA/pF) and Ba2+ current (IBa) density (7.3 +/- 0.5 pA/pF) compared with respective values of control myocytes (ICa,L) density 6.1 +/- 0.3 pA/pF, IBa density 11.3 +/- 0.8 pA/pF; P < 0.05). Endotoxemia-induced reduction in peak ICa,L could not be attributed to alterations in current-voltage relationships, steady-state activation and inactivation, or recovery from inactivation. The beta-adrenoceptor agonist isoproterenol, but not the Ca2+ channel activator BAY K 8644, reversed the LPS-induced reduction in peak ICa,L, cell contraction, and systolic [Ca2+]i. These data demonstrate that part of the host response to endotoxemia involves diminished sarcolemmal ICa,L of ventricular myocytes.

Action Potentials↗
PubMed1996

Effects of osmotically driven cell volume changes on diffusion-weighted imaging of the rat optic nerve.

The apparent diffusion coefficient (ADC) of the rat optic nerve was measured in vitro, using magnetic resonance imaging, to determine the effects of changes in cellular volume fraction on the diffusion of tissue water. Nerve ADC was determined under conditions of cell membrane depolarization and (i) increased intracellular volume, (ii) decreased intracellular volume, and (iii) negligible volume change. Depolarization alone had little affect on ADC, whereas volume changes produced strong, reversible effects. Increased cell volume decreased ADC and vice versa. These results are consistent with the view that changes in the extracellular space are the major source of ADC changes in brain tissue.

Animals↗
PubMed1996

The effects of cross-link density and chemical exchange on magnetization transfer in polyacrylamide gels.

The effects of polymer structure and water-macromolecule interactions on proton relaxation in an aqueous model polymer have been investigated using quantitative measurements of magnetization transfer. Polyacrylamide gels composed of 95% water, 5% comonomers acrylamide and N,N'-methylene-bis-acrylamide were studied. The structure and rigidity were varied by changing the cross-linking density of the polymer. The polymer showed a biphasic change in transverse relaxation with increasing cross-linking density which was accompanied by a sudden increase in magnetization transfer above 40% cross linking. This change may be attributed to the formation of rigid domains in the polymer which exhibit solid-like behavior with a short T2 (11 microseconds) and a Gaussian lineshape. Water-macromolecule interactions were controlled by varying the pH of the gel. At high pH (> 8), there was an increase in magnetization transfer and transverse relaxivity consistent with a chemical-exchange-mediated interaction between water protons and the polymer. By analyzing the system as two proton reservoirs coupled by magnetization exchange, the proton populations, intrinsic relaxation rates, and exchange rates were estimated, for different degrees of cross linking and pH. This model affords useful insights into the relevance of both supramolecular structure and chemical exchange on relaxation in tissues.

Acrylic Resins↗
PubMed1996

Tumor cell resistance to apoptosis due to a defect in the activation of sphingomyelinase and the 24 kDa apoptotic protease (AP24).

Signal transduction pathways involved in apoptotic cell death are poorly understood, although recent studies have implicated sphingomyelin hydrolysis and generation of the second messenger, ceramide. Previous work in this laboratory demonstrated that a serine protease termed AP24 was activated by TNF or UV light and induced DNA fragmentation in isolated nuclei. This study extended these findings to examine the role of these enzymes in apoptosis of the U937 cell line and the mechanism of resistance of its variant, U9-TR. Although this subclone was selected by growth in TNF, it was unexpectedly found to resist apoptosis induced by UV light, but was still sensitive to anti-Fas-induced DNA fragmentation. Here we show that in contrast to normal U937 cells, UV light and TNF both failed to activate neutral or acidic sphingomyelinase or AP24 in the U9-TR variant. However, anti-Fas activated both neutral and acidic sphingomyelinase in the variant comparable to that seen in parental U937. The U9-TR variant could be sensitized to TNF or UV light activation of both sphingomyelinase and DNA fragmentation by the protein phosphatase inhibitors okadaic acid and calyculin A. Furthermore, exogenous bacterial-derived sphingomyelinase caused U9-TR activation of AP24 and DNA fragmentation comparable to that in the parental U937. Exposure of permeabilized U937 cells to ceramide caused internucleosomal DNA cleavage that was blocked by an inhibitor of AP24. Taken altogether, these findings demonstrate that TNF or UV light activate sphingomyelinase that leads to the generation of ceramide resulting in activation of AP24 and DNA fragmentation in sensitive cells. A selective defect in signals leading to sphingomyelinase activation can confer resistance to apoptosis even though the variant is still sensitive to downstream apoptotic signals such as nuclear DNA fragmentation by activated exogenous AP24.

Apoptosis↗
PubMed1996

Effects of channel modulators on cloned large-conductance calcium-activated potassium channels.

Through expression of the cloned mouse (mSlo) or human (hSlo) large-conductance (BK) Ca(2+)-activated K+ channel in Xenopus laevis oocytes and HEK 293 cells, we characterized the effects of reported blockers and openers of BK channels to initiate the study of the molecular determinants of BK channel modulation. In oocytes, iberiotoxin and charybdotoxin, peptidyl scorpion toxins, were both equally effective blockers of BK current, although iberiotoxin was significantly more potent than charybdotoxin. The structurally related peptide kaliotoxin was not a potent blocker of BK current. Paxilline, a fungal tremorgenic alkaloid, was an effective but complex blocker of BK current. Tetrandrine, a putative blocker of type II BK channels, and ketamine were relatively ineffective. The putative BK openers NS004 and NS1619, phloretin, niflumic acid, flufenamic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) increased BK current in oocytes at microM concentrations; many of these produced biphasic concentration-response relationships. Coapplication of representative blockers and openers revealed several patterns of interaction, including competitive and noncompetitive antagonism. NS1619, niflumic acid, and phloretin were tested by using excised inside-out membrane patches from HEK 293 cells and were found to increase the activity of hSlo BK channels and produce a leftward shift in the G/Gmax-versus-voltage relationship of these channels. These results represent the first comprehensive examination of the molecular pharmacology of BK channels.

Alkaloids↗
PubMed1996

Use of subunit-specific antisense oligodeoxynucleotides to define developmental changes in the properties of N-methyl-D-aspartate receptors.

Antisense oligodeoxynucleotides were used to determine whether alterations in the expression of N-methyl-D-aspartate (NMDA) receptor subunit mRNA are responsible for developmental changes in the sensitivity of receptors to agonists and antagonists. Xenopus laevis oocytes were injected with mRNA prepared from neonatal and adult rat cerebral cortex, and the effects of agonists and antagonists were determined under voltage-clamp conditions. Glycine-site antagonists like 7-chlorokynurenate and glutamate-site antagonists like CGP-39653 were more potent at NMDA receptors expressed from mRNA from adult rat cerebral cortex than those expressed from mRNA from 1-day-old rat. NMDA receptors from 1-day-old rat cerebral cortex were more sensitive to activation by glycine than were receptors from adult rat cerebral cortex. 7-Chlorokynurenate and CGP-39653 were more potent inhibitors of responses seen with heteromeric NR1/NR2A receptors than with NR1/ NR2B receptors. Conversely, heteromeric NR1/NR2B receptors were more sensitive to activation by glycine than were NR1/NR2A receptors. We previously described a delay in the expression of the NR2A subunit in developing rat brain. Anti-sense oligodeoxynucleotides were used to determine whether the delayed expression of the NR2A subunit underlies changes in pharmacological properties observed during development. The properties of receptors seen when adult brain mRNA was coinjected with antisense oligodeoxynucleotides against the NR2A subunit were similar to those found in receptors from 1-day-old rat brain. These data suggest that changes in the sensitivity of NMDA receptors to antagonists and to glycine seen during development are a result of alterations in the expression of different species of NR2 subunit mRNA.

2-Amino-5-phosphonovalerate↗
PubMed1995

Barbiturate-reversible reduction of water diffusion coefficient in flurothyl-induced status epilepticus in rats.

Rat brains (n = 17) with flurothyl-induced status epilepticus (SE) have been imaged with a gradient-echo diffusion-weighted imaging sequence at 2.0 T. The apparent water diffusion coefficient (ADC) decreased during seizure discharges. The magnitude of the ADC reduction correlated well with the duration of flurothyl exposure. A 17% reduction in the water ADC compared with preseizure condition was observed in rats with the longest flurothyl exposure time. In 13 rats, pentobarbital was used to arrest the electrographic seizure activity. ADC values began to return to normal a few minutes after the injection. In four rats with no pentobarbital administration, ADC values remained depressed up to 1 h after seizure onset. The results suggest that diffusion-weighted MR imaging may be useful for mapping recent intense seizure activity in human patients with medically intractable epilepsy.

Animals↗
PubMed1995

Theoretical model for water diffusion in tissues.

Water diffusion in a tissue model is studied both analytically and numerically. Tissue is regarded as a periodic array of boxes surrounded by partially permeable membranes (cells), embedded in an extracellular medium. intracellular and extracellular diffusion coefficients may differ. Expressions for the apparent diffusion coefficients (ADC) in isotropic and nonisotropic tissues are derived and compared with Monte Carlo simulations. Calculated ADCs disagree with values obtained from the widely used "fast exchange" formula. Effects of differences between intracellular and extracellular T2 relaxation times on measured values of ADC and T2 are discussed. The general analysis is specifically applied to the changes occurring in ADC following ischemic insults to brain tissue. It is found that although membranes affect ADC significantly, the observed changes in diffusion cannot be due to reduced membrane permeabilities. They may result from the combined effect of changes in cellular volume fraction, extracellular and intracellular diffusion.

Acute Disease↗
PubMed1995

Anti-microbial activity of human CAP18 peptides.

BACKGROUND: CAP18 derived from rabbit leukocytes is a 142-amino acid protein recently demonstrated to have Lipopolysaccharide (LPS) binding and anti-microbial activity. The C-terminal 37 amino acids of rabbit CAP18 (CAP18(106-142) comprise the LPS-binding and anti-microbial domain. The homologous domain of human CAP18 (huCAP18(104-140) was identified from the recently cloned human CAP18 cDNA. OBJECTIVES: To evaluate the antimicrobial activity of C-terminal peptides derived from human CAP18. STUDY DESIGN: Prepare synthetic human CAP18(104-140) and study anti-microbial activity versus various gram-negative and gram-positive bacteria. RESULTS: Synthetic human CAP18(104-140) has broad anti-microbial activity versus both gram-positive (IC50 = 2.5 micrograms/ml) and gram-negative bacteria (IC50 = 0.5-5 micrograms/ml). Susceptible strains include Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium. A 32-amino acid peptide lacking five amino acids from the C-terminus of CAP18(104-140) has higher activity. Unlike previously characterized anti-microbial peptides derived from granulocyte proteins, CAP18(104-140) is active in serum. CONCLUSIONS: Human CAP18(104-140) or a derivative peptide may have therapeutic potential for bacterial sepsis.

Amino Acid Sequence↗
PubMed1995

Expression of mRNAs encoding subunits of the NMDA receptor in developing rat brain.

Developmental changes in the levels of N-methyl-D-aspartate (NMDA) receptor subunit mRNAs were identified in rat brain using solution hybridization/RNase protection assays. Pronounced increases in the levels of mRNAs encoding NR1 and NR2A were seen in the cerebral cortex, hippocampus, and cerebellum between postnatal days 7 and 20. In cortex and hippocampus, the expression of NR2B mRNA was high in neonatal rats and remained relatively constant over time. In contrast, in cerebellum, the level of NR2B mRNA was highest at postnatal day 1 and declined to undetectable levels by postnatal day 28. NR2C mRNA was not detectable in cerebellum before postnatal day 11, after which it increased to reach adult levels by postnatal day 28. In cortex, the expression of NR2A and NR2B mRNAs corresponds to the previously described developmental profile of NMDA receptor subtypes having low and high affinities for ifenprodil, i.e., a delayed expression of NR2A correlating with the late expression of low-affinity ifenprodil sites. In cortex and hippocampus, the predominant splice variants of NR1 were those without the 5' insert and with or without both 3' inserts. In cerebellum, however, the major NR1 variants were those containing the 5' insert and lacking both 3' inserts. The results show that the expression of NR1 splice variants and NR2 subunits is differentially regulated in various brain regions during development. Changes in subunit expression are likely to underlie some of the changes in the functional and pharmacological properties of NMDA receptors that occur during development.

Aging↗
PubMed1995

Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein.

CAP18 (18-kDa cationic antimicrobial protein) is a protein originally identified and purified from rabbit leukocytes on the basis of its capacity to bind and inhibit various activities of lipopolysaccharide (LPS). Here we report the cloning of human CAP18 and characterize the anti-LPS activity of the C-terminal fragment. Oligonucleotide probes designed from the rabbit CAP18 cDNA were used to identify human CAP18 from a bone marrow cDNA library. The cDNA encodes a protein composed of a 30-amino-acid signal peptide, a 103-amino-acid N-terminal domain of unknown function, and a C-terminal domain of 37 amino acids homologous to the LPS-binding antimicrobial domain of rabbit CAP18, designated CAP18(104-140). A human CAP18-specific antiserum was generated by using CAP18 expressed as a fusion protein with the maltose-binding protein. Western blots (immunoblots) with this antiserum showed specific expression of human CAP18 in granulocytes. Synthetic human CAP18(104-140) and a more active truncated fragment, CAP18(104-135), were shown to (i) bind to erythrocytes coated with diverse strains of LPS, (ii) inhibit LPS-induced release of nitric oxide from macrophages, (iii) inhibit LPS-induced generation of tissue factor, and (iv) protect mice from LPS lethality. CAP18(104-140) may have therapeutic utility for conditions associated with elevated concentrations of LPS.

Amino Acid Sequence↗
PubMed1995

[Effect of glucocorticoid receptor blockade on pulmonary and renal vascular permeability in scalded rats].

With glucocorticoid receptor (GR) blockade by RU38486, a competitive antagonist of GR, the change in contents of FITC labeled albumin (FITC-albumin) in pulmonary and renal tissue in scalded rats have been measured to study the changes in vascular permeability. The result showed that the contents of FITC-albumin in pulmonary and renal tissue in the scalded rats were markedly higher than those of the controls (lung: P < 0.05, kidney: P < 0.001). When the scalded rats were given GR blockade, the contents of FITC-albumin in pulmonary and renal tissue were significantly higher than those of rats with scald only (P < 0.05). The results indicated: (1) the pulmonary and renal vascular permeability in scalded rats was markedly enhanced; (2) GR blockade might aggravate the increase in vascular permeability caused by scald, so that the protective effect of glucocorticoid (GC) on vascular permeability seemed to be reversed.

Animals↗
PubMed1995

[The effects of glucocorticoid on rabbit polymorphonuclears during inflammation].

The CD18 expression on rabbit polymorphonuclears (PMNs) and adhesion rate of rabbit PMNs to ICAM-1 coated magnetic beads were determined, and the correlationship was analysed between CD18 expression and adhesion rate. The results showed that glucocorticoid inhibited the rise of CD18 expression on rabbit PMNs caused by tumor necrosis factor (TNF) and that the inhibitory effect reversed when glucocorticoid receptor (GR) was blocked by RU 38486. There was a positive correlationship (r = 0.966) after PMNs were cultured with a range concentration of dexamethasone (Dex). The data indicate that GC inhibits the rise of CD18 expression on rabbit PMNs caused by TNF which is mediated by GR, and plays an important role in inhibition of PMNs adhesion.

Animals↗
PubMed1995

[High purification of human thrombin].

A highly purified human thrombin was prepared from plasma. The procedure involved the adsorption of prothrombin from human plasma by barium chloride and precipitation by using ammonium sulfate. The partially purified prothrombin was activated by tissue thromboplastin and followed by chromatography on Amberllte and SP-Sephadex. The purified enzyme is homogeneous on SDS-PAGE and has a specific activity toward fibrinogen of 2000 NIH U/mg. The recovery is about 30% approximately 40%. This highly purified human thrombin can be used as a tool enzyme in the downstream procedure of fused recombinant proteins expressed by genetic engineering.

Amino Acid Sequence↗